miR-455-3p Is Negatively Regulated by Myostatin in Skeletal Muscle and Promotes Myoblast Differentiation

Abstract

Myostatin (MSTN) is a growth and differentiation factor that regulates proliferation and differentiation of myoblasts, which in turn controls skeletal muscle growth. It may regulate myoblast differentiation by influencing miRNA expression, and the present study aimed to clarify its precise mechanism of action. Here, we found that MSTN −/− pigs showed an overgrowth of skeletal muscle and upregulated miR-455-3p level. Intervention of MSTN expression using siMSTN in C2C12 myoblasts also showed that siMSTN significantly increased the expression of miR-455-3p. It was found that miR-455-3p directly targeted the 3′-untranslated region of Smad2 by dual-luciferase assay. qRT-PCR, Western blotting, and immunofluorescence analyses indicated that miR-455-3p overexpression or Smad2 silencing in C2C12 myoblasts significantly promoted myoblast differentiation. Furthermore, siMSTN significantly increased the expression of GATA3. The levels of miR-455-3p were considerably reduced in C2C12 myoblasts following GATA3 knockdown. Consistently, GATA3 knockdown also reduced the enhanced miR-455-3p expression caused by siMSTN. Finally, we illustrated that GATA3 has a role in myoblast differentiation regulation. Taken together, we identified the expression profiles of miRNAs in MSTN −/− pigs and found that miR-455-3p positively regulates myoblast differentiation. In addition, we revealed that MSTN acts through the GATA3/miR-455-3p/Smad2 cascade to regulate muscle development.

Adipocyte-derived exosomes from obstructive sleep apnoea rats aggravate MASLD by TCONS_00039830/miR-455-3p/Smad2 axis

“…MiR-455-3p can improve lipid metabolism in the liver by inhibiting the suppressor of cytokine signalling 3 through SREBP-1c 25 , 26 . Han et al confirmed that the GATA3/miR-455-3p/ Smad2 cascade is involved in regulating muscle development in C2C12 myoblasts 27 . MiR-455-3p inhibited the activation of hepatic stellate cells by targeting the Hsp47/TGF-beta/Smad4 signalling pathway and was recommended as a promising therapeutic target for liver fibrosis 28 .…”

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

“…One of these MSTN -edited models, its progeny, or its crosses were further investigated . These include investigations on fiber-type distribution and expression of myosin heavy chain isoforms; shift from slow- to fast-twitch muscle fibers in skeletal muscle; internal organ size; semen quality and fertilization ability; reproductive trait characterization in MSTN -edited crosses; collagen-related pathological features (umbilical hernia and tippy toe standing); regulation of body fat deposition; fibrinogen levels and fibrin clot structure; esophageal striated muscle development and regulation of muscle fiber types; extraocular muscles; cardiac extracellular matrix; growth of smooth muscle in uterine horns of MSTN mutant gilts; smooth muscle content in corpus cavernosum of MSTN mutant boars; erythrocyte osmotic fragility, hematological parameters, and fatty acid composition of serum and erythrocyte membranes; miR-455-3p regulation of myoblast differentiation; composition and alteration of gut microbiota; analysis of meat and fatty acids characteristics; and development of a restriction enzyme-mediated PCR-RFLP assay for genotyping MSTN mutant pigs …”

The Landscape of Accessible Chromatin and Developmental Transcriptome Maps Reveal a Genetic Mechanism of Skeletal Muscle Development in Pigs

“…They also play a regulatory role in self-renewal and cell proliferation. Moreover, the MYH3 gene can affect muscle fiber type composition and intramuscular fat content in pigs [ 24 , 25 ], and myostatin ( MSTN ) can negatively regulate skeletal muscle growth and development through autocrine or paracrine signaling [ 13 , 26 ]. In addition, skeletal muscle development is associated with epigenetic regulatory mechanisms [ 27 ].…”